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New Discovery May End Transplant Rejection
mmmscience writes with this excerpt from the Examiner:
"Big news in the medical world: scientists in Australia have found a way to stop the body from attacking organ transplants, greatly decreasing the possibility of organ rejection. ... When a new tissue is introduced, one's immune system kicks into overdrive, sending out cells known as killer T cells to attack and destroy the unknown tissue. ... Professor Jonathan Sprent and Dr. Kylie Webster from Sydney's Garvan Institute of Medical Research focused on a different type of T cells — known as regulatory T cells (Treg) — in this study. Tregs are capable of quieting the immune system, stopping the killer T cells from seeking out and attacking foreign objects."
Okay, what does that do for fighting off infection then?
It's not like there's a magical component to this that identifies the transplanted material as "good" and infectious agents as "bad".
Chas - The one, the only.
THANK GOD!!!
This will make organlegging possible. If you can just grab any kidney off the street and use it to replace a failing one, people will.
All ideas^H^H^H^H^Hprocesses in this post are Patent Pending. (as well as the process of patenting all postings)
As someone about to donate a kidney this summer, I really hope they work on this research more. Donor matching is incredibly difficult, and the risk of rejection poses issues not only with the health of the recipient (though that's obviously the major issue), but also with the psychological health of the donor. A failed donation can make you feel like crap.
In the end, yes.
simon
Now i can just keep smoking knowing my new lungs will fit in no problem! /s
Well, you can, but that would be like having a Core2Duo for just reading emails...
simon
But it only is needed for 2-3 weeks, according to the article. Just long enough for the body to accept the new cells, after that they let things go back to normal, which would allow the body to attach infectious agents.
The idea (as I understand it) is this:
1) Immunosuppressants not only lower your defenses but are also toxic (as with many drugs).
2) I assume the treatment is either non-toxic, or at least not as bad for you.
3) Not sure about this: I think that people need to take immunosuppressants for a LONG time after the transplant, thus pumping in toxins AND keeping the defenses low, where as this idea is a one time thing you do before the transplant and are then done with.
The wording also makes it sound like the rejection rate is lower than usual, I am unsure if this is true or not.
So yes, you still have the lowered defenses, but with out the toxins, and possibly for a shorter time.
Do Or Do Not, There Is No Spoon, There Is Only Zuul. Everything in the above post is probably opinion.
TFA and TF summary are missing the "if"s.
Yes this could be a big deal, someday, if the finding holds up for other mammals (a big one), if it works for different kinds of transplants, if it's repeatable, if there are no other major consequences, if human trials are successful, if if if.
Failure to include the "if"s is misleading at best and irresponsible at worst, for giving possibly false hope to those dealing with transplant rejection.
If only there was a linked article that addressed these questions!
I assume you were goign to say "we might know how to reverse it".
The answer is fairly simple:
We are giving (and have been for a long time) people something like AIDS, not AIDS itself as that is a condition directly linked to HIV (even though the name makes it sound like it would be any time when you acquire a immune deficiency). It isn't AIDS we need a treatment for, it is HIV.
Do Or Do Not, There Is No Spoon, There Is Only Zuul. Everything in the above post is probably opinion.
I'm glad that joke didn't swing the other way.
I have been having problems with my hyperalloy combat chassis rejecting the external skin tissue overlays. I am making kill^H^H^H^H pet robots and this is just the trick I needed,
I wonder if this could help in regards to allergies? I.e. stop the immune system from "reacting" too much?
And in those 2-3 weeks they keep the person in a steril room devoid of any potential bacteria/virus' that could harm the person.
Hopefully they will be able to run positive clinical trials in the future. So far this is only effective on mice on relatively simple procedures (skin grafts, and pancreatic transfers). Kidneys, hearts, lungs are huge deals. I'm assuming if this hurdle is passed the doner would only need to have a blood-type match? That would be awesome and would make the waiting list that much simpler.
I do not support "The Man". I also do not support your irrational stupidity
Yeah... or buying a SUV to get your groceries. Oh, wait...
My 0.02 cents
"3) Not sure about this: I think that people need to take immunosuppressants for a LONG time after the transplant"
AFAIK ('tho there're bound to be exceptions maybe?) - you take them for as long as you don't want your immune system to attack the new organ, which'll basically be, for the rest of your life.
The revolution will not be televised... but it will have a page on Wikipedia
For starters "killer T-cells" are usually referred to as NK-cells and they are NOT thought to be part of the normal rejection process (they do not require activation and thus would no be stopped by immunosuppresion). There are three types of rejection hyperacute (pre-formed antibodies attack the organ in minutes - the organ literally dies as soon as it is transplanted - this is avoided by the "matching" process), acute (where T-cells [not NK-cells] attack the organ since it is not "self" and therefore "bad" - this is where immunosuppresion helps) and chronic (the body slowly rejects by allowing fibrosis of the vessels leading to the organ).
Actual survival statics for all kidney allografts exceeds 95% today. 80% is quite a drop!
Grafts are not assumed to "take" after 100 days allowing us to stop immunosuppresion! Immunosuppression is currently LIFELONG. There are a few instances where people have tolerated a non-identical twin transplant without medications, but this is _very_ rare. There is active research into finding the key to allow "tolerance" whereby we can drop the medications, but this is still early.
IL-2 suppression is the _mainstay_ of current immunosuppressants both blocking its production via calcineurin ihibitors (cyclosporin and tacrolimus), inhibiting the response (sirolimus/rapamune), or by blocking the receptor with antibodies (basiliximab/daclizumab). (Please understand this is only about half of the therapies that are in use for immunosuppresion, I'm just focusing on the Il-2 aspect).
Just followed the second link and it is _much better_. Still, I strongly disagree with their assertions of 100 days, just doesn't happen in humans. Apparently this study is using IL-2 STIMULATION with a complex that attempts to increase the regulatory T-cells...To me this means that this treatment will not co-exist with the current immunopupression dogma... this means that they will have to have a "complete" replacement for immunosuppresion they won't be able to add this to the current regiment and that means this treatment protocol will be quite sometime in the pipeline. And (fortunately) the authors acknowledge that they are optimistic, but aren't rushing off to collect their Nobel yet:
I am also aware that effective approaches in mice do not necessarily give good results in humans because of subtle differences in the immune systems of mouse and man.
1.) Correct.
:D
2.) Also correct.
Immunosuppressant drugs, besides increasing the risk of infection and cancer, also screw with the kidneys, liver, and pancreas. So besides the fun 1-2 punch of increased risk of infection post-surgery and having a weaker immune system to fight it with, you can also have a delightful bouquet of metabolic issues to go with it. This treatment seems to take the "traffic control" route, instead of mass-nuking the entire T-cell population.
3.) If the rejection is hyperacute (immediate) or acute (several days to weeks after transplant), it's treatable. Chronic rejection, though, is irreversible and requires a lifetime of immunosuppressants. Exception: if bone marrow can also be transplanted, this effectively replaces the recipient's immune system with the donor's, so there is no rejection.
Overall, this looks pretty damn promising. If they could also figure out what happened with Demi-Lee Brennan, we'd be well on our way to Bioshock-style instant upgrades
3) Not sure about this: I think that people need to take immunosuppressants for a LONG time after the transplant, thus pumping in toxins AND keeping the defenses low, where as this idea is a one time thing you do before the transplant and are then done with.
My father had a lung transplant about 5 years ago. You have to take the immunosuppressants forever with any inner body transplant (like heart, kidney, lung, etc). The immunosuppressants are quite good, but their side effects are significant and effect the life of a person. My father had to take significant amounts of pills daily at very specific times for everything to work properly. The pills also place quite a strain on the kidneys.
Bizarrely enough, that's what eventually killed him. The doctors (who, BTW, were outstanding) switched him to an immunosuppressant that was less stressful on his kidneys. The new drug had one very rare side effect that would eventually cause death. Dumb father didn't tell them he was having problems with new drug until it was too late and his body rejected the lung killing him. But Dad got 5 extra years that we wouldn't have had otherwise.
And the article is wrong about one point. The biggest problem for transplant recipients is not the drugs themselves. I.E. the effects on the body. That's bad. What's worse is the cost of the drugs and all the associated aftercare. The costs of the drugs are so great that unless one has a quite good insurance policy or a small fortune, your going to lose just about one's entire worth to pay for drugs. To me that's the second great advantage to this finding.
BTW, if anyone out there is looking for an outstanding lung transplant program, the program at Cedar Sinai Medical Center in Los Angeles is fantastic. The doctors are great, the support staff is first rate, and the care they give you is outstanding.
And in those 2-3 weeks they keep the person in a steril room devoid of any potential bacteria/virus' that could harm the person.
Depending on the transplant, you're probably not going to want to do anything other than lie in a bed during that time anyway.
3) Not just a LONG time -- for as long as you have the transplant.
I got a kidney transplant in 1995, and I will be on anti-rejection drugs until either 1) I die, 2) something better comes along that doesn't require anti-rejection meds anymore (<crosses fingers>), 3) or I reject the kidney and it is removed.
MCSE? No, sir...I don't do Windows. Yes, I am an idealist. What's your point?
Is caused by the immune system not recognizing a foreign invader, the organ being transplanted.
No?
No. Rejection is the appropriate response by the body. With immunsuppresion, we modulate that response.
Then this guy wants to turn off that ability in the body?
Yes?
No, not quite. Their proposal is to stimulate the immune system, but to add this "complex" that says "It's ok...don't attack"
Historically speaking, whenever doctors have taken that approach it results in massive infection, and usually heart and lung problems.
Well, if that were the case, most of the transplant pt's would be dead. Obviously you have taken this a little to far (reduce ad absurdum). First, keep in mind there are two major (humoral aka antibody mediated and c-mediated) and several minor arms to the immunesystem. The humoral system is relative untouched by immunosuppression while the cell-mediated system is what is modulated, but not turned off. And yes there is a risk of infection with immunosuppresion, but not as much as you might expect. The trick to turn off just enough of the immune system to allow the graft to survive, but not enough to endange the patient.
You would think after so many complications from transplants, they would stop pursuing that direction.
Well there are risks, but quality and quantity of life are better with transplant. Kindey failure itself increases the risk of infection, causes chronic refractory anemia (often requiring frequent transfusions) and increases the risk of heart disease. Hemodialysis (filtering the blood to replace kidney function) requires most people to be hooked to a machine for 3-4 hours three times a week (during business hours!). These patients often undergo numerous surgeries to create or correct the vascular access required to get HD. The HD process itself is very draining.
Liver failure really sucks. You can become encephalopathic (an altered mental state typically confusion and altered sleep cycles), you become coagulopathic (bleed easily), you can develop varices (dilated venin in the esophagus, abdominal wall, rectum, etc) which can bleed and are a bitch to stop when you are coagulopathic. Liver failure is deadly with or without treatment. Kidney failure is also deadly, but with HD you can susrvive.
Adult stem cell research seems to be the best approach to me. Same tissue so no rejection, and they do not have all of the problems fetal cells have. (i.e. Fetal stem cells have a nasty habit of becoming tumors.)
Somehow, Adult stem cells "know" what to do and when to stop growing appropriately much better than fetal stem cells when considering tissue regeneration in heart attack patients for example.
I agree that stem cells and gene therapy are our ideal goals but with the state of the art being the equivalent of trying to park your car by dropping it into the city at 50,000 ft (15240 m) we still have a long way to go. In the mean time, transplants remain a sound medical treatment
Not that doctors understand any of this process, but why they continue to invest so much money in transplant research is baffling. The quality of life for people financially and medically sucks for current transplant recipients.
For the majority, you are quite ill-informed. Most patients are quite happy with their transplants and their quality of life improved markedly. Also, kidney transplants that last 5 years are more economical than being on dialysis for that time period. This is why insurance companies actually pay for transplants.
This is better news than they even let on. A means to control rejection is the same as a means to control autoimmune disorders. Recent evidence supporting this is at http://www.ncbi.nlm.nih.gov/pubmed/19199937 There's a partial list of such disorders at http://en.wikipedia.org/wiki/Autoimmune_disease
Knowing the mechanism for increasing Treg leads to understanding the mechanism for controlling, thus including suppressing Treg. That would boost the body's immune response. It could control (though not cure) AIDS, and lead to treatments of such as hepatitis B or C without requiring the very side effect laden pegylated alfa interferon 2 + ribavirin treatment. Inducing autoimmnune disease has already been suggested as a cancer treatment http://www.pnas.org/content/96/10/5340.full
As explained in http://en.wikipedia.org/wiki/Immune_system an immune system is a very complex system with many components that interact. The more of these we can manipulate the closer we get to the kind of treatments suggested above.
"I may be synthetic, but I'm not stupid." -- Bishop 341-B
Well, IANAD, but as far as I understand it, not only does the new bone marrow generate T-cells (among other blood cells), its "offspring" take up residence in organs, so basically it's a complete reboot of the immune system, including bloodstream and organ tissues. As a matter of fact, it's such a "clean slate" that recipients lose their acquired immunity, and all the vaccinations (polio, measles, etc.) have to be done again.
I'm guessing the problem isn't that sterilizing a place is so expensive. There would be the increased cost of doing buisness in a sterile place (autoclaving absolutely everything, scrubbing and suiting up if you're entering), but the two biggest costs by far I would assume to be verifying the cleanliness and (even bigger) liability and insurance for failure to maintain sterility.
I worked at a large phamecutical plant on a microbiology team ensuring that their clean room facilities were actually clean. Extremely boring work, but the worst part was that if and when you messed up (even in a trivial way like not using fresh batteries on the fans to sample the air for bacterial growth every single time) there was a mountain of paperwork to be filled out, explaining why you failed, how you're going to ensure you don't fail again, and assesing whether or not it was going to compromise anything important. An absurd amount of red tape. The actual monitoring of the sterility was extremely easy.
So that's a gigantic cost right there. I know nothing about the liability side to it other than I'm sure there are thousands of lawyers who would salivate at the thought of a patient dying after a transplant because of an infection during the 2 week sterile cycle.
And keep in mind that hospitals charge you about 10 dollars for an asprin...